The determination of cardiac output, or measurement of the blood volumetric output of the heart is of substantial importance for a variety of medical situations. Intensivists utilize such information along with a number of additional pulmonary factors to evaluate heart patients within intensive care units. A variety of approaches have been developed for measuring this output, all of which exhibit certain limitations and/or inaccuracies. In effect, the volumetric aspect of cardiac output provides information as to the sufficiency of oxygen delivery to the tissue or the oxygenation of such tissue. When combined with other measurements, an important evaluation of the status of the cardiovascular system of a patient may be achieved.
Currently, the more accepted approach for deriving cardiac output values is an indicator dilution technique which takes advantage of refinements made earlier in pulmonary catheter technology. With the indicator dilution approach, a signal is inserted into the blood upstream from the pulmonary artery, and the extent of signal dilution can then be correlated with stroke volume or volumetric output of the heart. Of these indicator dilution methods, thermodilution is the present technique of choice, and in particular, that technique employing a cold liquid injectate as the signal This approach necessarily is invasive, requiring placement of a Swan-Ganz type pulmonary artery catheter such that its tip or distal end functions to position a temperature sensor just beyond the right ventricle within the pulmonary artery. The indicator employed is a bolus of cold isotonic saline which is injected from the indwelling catheter into or near the right atrium. Downstream blood temperature then is monitored to obtain a dilution curve relating temperature deviation to time, such curves sometimes being referred to as "wash out" curves. Combining the area under this thermodilution curve with the amount of energy subtracted by cooling of the blood provides a measure of the rate at which the heart is pumping blood, such rate usually being expressed in liters per minute. If cardiac output is high, the area under the thermodilution curve for a given applied energy, Q, will be relatively small in accordance with the well-known Stewart-Hamilton relationship. Conversely, if cardiac output is low, the area under the thermodilution curve for a given amount of applied energy, Q will be relatively large. See in this regard:
Ganz, et al., "A New Technique for the Measurement of Cardiac Output by Thermodilution in Man," American Journal of Cardiology, Vol. 27, April, 1971, pp 392-396. PA1 Afonzo, S., et al.., "Intravascular and Intracardiac Blood Temperatures in Man," Journal of Applied Physiology, Vol. 17, pp 706-708, 1962. PA1 "Instantaneous and Continuous Cardiac Output Obtained with a Doppler Pulmonary Artery Catheter," Journal of the American College of Cardiology, Vol. 13, No. 6, May, 1989, pp 1382-1392. PA1 "Transtracheal Doppler: A New Procedure for Continuous Cardiac Output Measurement," Anesthesiology, Vol. 70, No. 1, Jan. 1989, pp 134-138. PA1 "Continuous Cardiac Output Monitoring During Cardiac Surgery," Update in Intensive Care and Emergency Medicine, Berlin: Springer-Verlag, 1990, pp 413-417. PA1 "Alternatives to Swan-Ganz Cardiac Output Monitoring" by Moore, et al., Surgical Clinics of North America, Vol. 71, No. 4, Aug. 1991, pp 699-721. PA1 Shippey, C. R., Appel, P. L., Shoemaker, W. C., "Reliability of Clinical Monitoring to Access Blood Volume in Critically Ill Patents", Critical Care Medicine, Vol. 12, No. 2, pp 107-112 (1984) PA1 Silbergleit, Schultz, et al, "A New Model of Uncontrolled Hemorrhage that Allows Correlation of Blood Pressure and Hemorrhage", Academic Emergency Medicine, Vol. 3 No. 10, pp 917-921 (1996). PA1 Dagher et al, "Blood Volume Measurements: A Critical Study. Prediction of Normal Values: Controlled Measurement of Sequential Changes: Choice of a Bedside Method", Advances In Surgery 1969; 1:69-109.
In a typical procedure, a cold bolus of saline at ice or room temperature in an mount of about 5-10 milliliters is injected through the catheter as a measurement procedure which will require about two minutes to complete. For purposes of gaining accuracy, this procedure is repeated three or four times and readings are averaged. Consequently, the procedure requires an elapsed time of 4-5 minutes. In general, the first measurement undertaken is discarded inasmuch as the catheter will have resided in the bloodstream of the body at a temperature of about 37.degree. C. Accordingly, the first measurement procedure typically is employed for the purpose of cooling the dilution channel of the catheter, and the remaining measurements then are averaged to obtain a single cardiac output value. Thus, up to about 40 ml of fluid is injected into the pulmonary system of the patient with each measurement which is undertaken. As a consequence, this procedure is carried out typically only one to two times per hour over a period of 24 to 72 hours. While practitioners would prefer that the information be developed with much greater frequency, the procedure, while considered to be quite accurate, will add too much fluid to the cardiovascular system if carried out too often. Of course, the accuracy of the procedure is dependent upon an accurate knowledge of the temperature, volume, and rate of injection of the liquid bolus. Liquid volume measurements during manual infusions are difficult to make with substantial accuracy. For example, a syringe may be used for injecting through the catheter with the result that the volume may be identified only within several percent of its actual volume. Operator error associated with volume measurement and rate of injection also may be a problem. Because the pulmonary catheters employed are somewhat lengthy (approximately 30 to 40 inches), it is difficult to know precisely the temperature of the liquid injectate at the point at which it enters the bloodstream near the distal end of that catheter. Heat exchange of the liquid dispensing device such as a syringe with the catheter, and the blood and tissue surrounding the catheter upstream of the point at which the liquid is actually released into the blood may mean that the injectate temperature is known only to within about five percent of its actual temperature. Notwithstanding the slowness of measurement and labor intensity of the cold bolus technique, it is often referred to as the "gold standard" for cardiac output measurement by practitioners. In this regard, other of determining cardiac output typically are evaluated by comparison with the cold bolus approach in order to determine their acceptability.
Another technique of thermodilution to measure cardiac output employs a pulse of temperature elevation as the indicator signal. In general, a heating coil is mounted upon the indwelling catheter so as to be located near the entrance of the heart. That coil is heated for an interval of about three seconds which, in turn, functions to heat the blood passing adjacent to it. As is apparent, the amount of heat which can be generated from a heater element is limited to avoid a thermocoagulation of the blood or damage to tissue in adjacency with the heater. This limits the extent of the signal which will be developed in the presence of what may be considered thermal noise within the human body. In this regard, measurement error will be a result of such noise phenomena because of the physiological blood temperature variation present in the body. Such variations are caused by respirations, coughing, and the effects of certain of the organs of the body itself. See in this regard:
See also, U.S. Pat. No. 4,595,015.
This thermal noise-based difficulty is not encountered in the cold bolus technique described above, inasmuch as the caloric content of a cold bolus measurement is on the order of about 300 calories. By contrast, because of the limitations on the amount of heat which is generated for the temperature deviation approach, only 15 or 20 calories are available for the measurement. Investigators have attempted to correct for the thermal noise problem through the utilization of filtering techniques, for example, utilizing moving averages over 6 to 12 readings. However, where such corrective filtering approaches are utilized, a sudden downturn in the hemodynamic system of a patient will not be observed by the practitioner until it may be too late. The effective measurement frequency or interval for this technique is somewhat extended, for example about 10 minutes, because of the inaccuracies encountered. In this regard, a cardiac output value is achieved only as a consequence of a sequence of numerous measurements. In general, the approach does not achieve the accuracy of the above-discussed cold bolus technique. Thermodilution techniques involving the use of electrical resistance heaters are described, for example, in U.S. Pat. Nos. 3,359,974; 4,217,910; 4,240,441; and 5,435,308.
Other approaches to the elimination of an injectate in thermodilution procedures have been, for example, to introduce the thermal signal into the flowing blood by circulating a liquid within the catheter, such liquid preferably being cooler than the blood temperature. See in this regard, U.S. Pat No. 4,819,655. While, advantageously, no injectant is utilized with such procedure, the method has the disadvantage that only a limited thermal signal is available as compared with the cold bolus approach, and, thus, the measurement is susceptible to error due to physiological temperature variations. As another example, a technique has been proposed wherein a stochastic excitation signal present as a series of thermal pulses of varying duration is inserted within the bloodstream, and the resultant output signal downstream, now present as blood temperature variation, is measured. The blood flow rate then is extracted by cross-correlating the excitation signal and measured output signal. See U.S. Pat. No. 4,507,974.
Dilution and conductivity dilution techniques, also involving injection of an auxiliary liquid such as a dye or saline solution into the bloodstream are known. See in this regard, U.S. Pat. Nos. 3,269,386; 3,304,413; 3,433,935; 3,820,530; 4,572,206; and 5,092,339. A resulting dye dilution or conductivity dilution curve will be seen to be similar to the above-discussed thermodilution curve. Dye dilution and conductivity dilution procedures exhibit certain of the deficiencies discussed in connection with the injected liquid bolus-based thermodilution approach, namely difficulty in precisely controlling the rate of manual injection and measuring the injectate volume as well as an unsuitability of the procedure for frequent or repeated use over long periods of time. The above-noted dye dilution procedures have been employed for a relatively extensive period of time. In general, a dye is injected into the bloodstream and then a blood sample is drawn, typically from a major artery, at various intervals of time. The technique is quite labor intensive and, because of the extensive amount of dye which is required to obtain an accurate measurement. the frequency of measurement is very low. In particular, if the frequency is attempted to be enhanced, then the signal-to-noise ratio encountered becomes unacceptable as the background color of the blood continues to change. The saline solution approach involves the injection of a hypertonic saline solution having a much higher salt content per unit volume than, for example, typical isotonic saline solution which is about 0.9% sodium chloride. Following injection of the hypertonic saline solution, the electrical resistivity of the blood is evaluated. The method has been criticized inasmuch as such an extensive amount of electrolyte is added to the blood for each measurment, the electrolyte balance in the body becomes adversely affected. Note that the technique looks at electrical charges in a direct fashion as they exist in the bloodstream. Another indicator-dilution method for determining cardiac output involves, the utilization of a cation, preferably lithium, which is not already present in the blood. This cation is injected as a bolus into the blood. A cation selective electrode is used to measure concentration and subsequently develop a resulting cation dilution curve in a manner similar to a thermodilution measurement. Cation-dilution cardiac output measurement methods share certain of the same deficiencies as discussed above for liquid-bolus-based thermodilution methods. See U.S. Pat. No. 5,395,505.
Ultrasonic echocardiography has been employed for the instant purpose. With this invasive method, a plurality of microbubbles is introduced into the blood upstream of the measurement position. As described in U.S. Pat. No. 4,316,391, an ultrasonic pulse is generated from a position opposite and spaced from the region of the flowing microbubbles, for example, using an ultrasonic transducer/receiver located outside of the body. A reflective ultrasonic image, created by reflection of the ultrasonic pulse from the microbubble dispersions is measured and correlated with cardiac output, i.e. flow rate, using conventional dilution techniques. This method preferably employs microbubbles comprising a gelatin membrane-encased "inert" gas such as nitrogen or carbon dioxide to perform each measurement. As a consequence, the method is not suitable for performing clinical measurements continuously or even intermittently for an extended period of time due to the accumulation of bubble membrane material that must be cleared from the body by the body's own cleansing processes.
A derivation of cardiac output by simultaneously measuring blood velocity and vessel geometry has been described, for example, in U.S. Pat. Nos. 4,733,669 and 4,869,263. With this approach, a Doppler pulmonary artery catheter system is provided which develops instantaneous vessel diameter measurements and a mapping of instantaneous blood velocity profiles within the main pulmonary artery. From such data, an instantaneous cardiac output then is calculated. See in this regard the following publication:
A similar approach has been described which involves a technique wherein a piezoelectric ultrasound transducer is placed in the trachea of a patient in proximity to the aorta or pulmonary artery. Ultrasound waves then are transmitted toward the path of flow of blood in the artery and are reflected and received. The cross-sectional size if the artery is measured, based upon the Doppler frequency difference between the transmitted and received waves. Imaging techniques such as X-ray or radioisotopic methods also have been used. See generally the following publication:
See additionally, U.S. Pat. Nos. 4,671.295 and 4,722,347.
A pulse contour technique for measuring blood velocity which requires a secondary calibration is described in the following publication:
Another approach employs a so-called "hot wire" anemometer or heated thermistor as described in U.S. Pat. No. 4,841,981; EP 235811; U.S. Pat No. 4,685,470, and W088/06426.
Any of the velocity-based measurement techniques for deriving cardiac output confront a rather basic difficulty not present with indicator dilution approaches. That difficulty resides in the necessity for knowing the geometric cross section of the vessel through which blood is flowing. In this regard, the geometry and diametric extent of the pulmonary artery is not known and is dynamic, changing with the pulsation nature of blood flow. Of course, the velocity measurements themselves must account for the surface effect of the interior of the vessel, velocity varying from essenially a zero value at the interior surface or lumen of the vessel to a maximum value towards the interior of that vessel.
A non-invasive technique evaluating thoracic electrical bioimpedance to derive cardiac outputs has been studied, for example, using electrocardiographic signals (ECG). However, cross-correlation of the results with the well-accepted thermodilution technique have led to questions of reliability.
For a general discourse looking to alternatives to the current indicator dilution method of choice, reference is made to the following publication:
A correlate to the diagnostic, cardiac output (CO) is the corresponding value for total circulating blood volume (CVB). The first and most important therapeutic goal for hemorrhagic, post operative, cardiogenic, traumatic, neuogenic for septic shock is to restore blood volume to normal levels. Determining blood volume, however, has been an elusive undertaking. Typically, other hemodynamic parameters such as mean arterial pressure (MAP), wedge pressure (WP) or occlusion pressure, central venous pressure (CVP) and hematocrit (Hct) are used by clinicians to infer blood volume. However, such inferentially based approaches do not accurately reflect blood volume except at more extreme departures from normal levels. See in this regard:
A broad variety of patient conditions are associated with the abnormal blood volume levels referred to as "hypovolemia" (circulating volume too low) and "hypervolemia" (circulating volume too high). Hypovolemia occurs commonly during surgery and represents a significant cause of intestinal hypoperfusion. Hypoperfusion occurs as a response to any reduction in circulating blood volume as blood is directed away from the intestinal vascular bed in favor of vital organs. Management of circulating blood volume is essential prior to, during and following cardiopulmonary bypass procedures, inasmuch as avoiding hypovolemia improves organ perfusion and reduces morbidity and mortality. Circulating blood volume data also is important for carrying out the treatment of patients with ruptured cerebral aneurysms who often are hypovolemic. Hemorrhegic shock following traumatic injury is caused by extensive blood loss or blood loss induced trauma in the central nervous system. Failure to recognize the presence or extent of blood loss is an important factor in avoiding the loss of the patient. While hypotensive injury victims routinely receive rapid fluid resuscitation, an excessive addition of fluid into the vascular system may increase bleeding and worsen the outcome, see:
Hypovolemia is one of the principal defects contributing to cardiovascular instability and circulatory failure during septic shock. During sepsis, microcirculation often is severely impaired to exacerbate the problem of hypervolemia. Hypovolemia-induced hypotension is reported to complicate approximately 30% of all dialysis treatments. Short duration hemodialysis involving ultra filtration can cause hypovolemia unless corrective action is taken such as reducing the filtration rate or interrupting the hemodialysis process to allow for compensatory changes in the patients circulating blood volume. Acute renal failure occurs most commonly in a setting of surgery and trauma due to hypovolemia, sepsis, obstetric complications, hemolytic reaction and poisoning. A principal challenge to practitioners treating burn patients is the management of circulating blood volume in the presence of excessive plasma loss at the burn sites. Hypovolemia is a common complication of patients with burns.
Conventional methods for measuring circulating blood volume depend typically upon the dilution of a dye, radioactive tracer or other analyte which, following injection is mixed into the bloodstream. Blood volume then is calculated, inter alia, from the extent of dilution and such calculation assumes that the indicator-analyte is immisible in red blood cells.
In order to estimate total circulation blood volume (TCBV), i.e., the summation of plasma volume (PV) and red blood cell volume (RBCV), the large vessel hematocrit (LVH) also is measured so that total blood volume is obtained by the following relationships: ##EQU1##
The most accurate method for measuring total blood volume avoids the potential error of using the large vessel hematocrit value (which is not representative of the hematocrit throughout the circulatory system) by separately measuring the plasma volume and red blood cell volume. This method is known as the Summation Method. See generally:
As has been reported in the literature since 1941, of the various radionuclides employed, a technique utilizing .sup.51 Cr has been considered a "gold standard" for deriving circulating blood volume values. However, this approach, as well as dye-based dilution approaches are both costly and are limited to relatively infrequent measurement. As a consequence, a continuous monitoring of blood volume changes or trending-type monitoring has not been available to practitioners. A more recent approach, utilizing .sup.131 I as a radiolabel provides for the obtaining of a plurality of blood samples over 20-35 minutes following tracer injection. Tracer dilution is combined with hemocrit to calculate blood volume. See in this regard: U.S. Pat. Nos. 5,024,231 and 5,529,189. In general, this approach has been problematic in terms of cost, limitations on the number of measurements which can be made, and the inherent procedure and physiologic limitations associated with the radionuclide.
Practitioners involved in the management of more critical hemodynamic conditions, typically turn to commonly monitored and thus more immediately available parameters such as mean arterial pressure (MAP), pulmonary catheter wedge pressure (PCWP), central venous pressure (CVP), heart rate (HR) and hematocrit (HCT) to estimate or infer a value for total circulating blood volume. Studies have shown, however, that such inference-based determinations are prone to error.